1. Glycation alters the mechanical behavior of kidney extracellular matrix
- Author
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Sarah Dillender, Nicholas Ferrell, Dan Wang, Rishabh Agarwal, and Snehal Sant
- Subjects
Histology ,Biophysics ,Matrix (biology) ,Kidney ,Biochemistry ,Article ,Extracellular matrix ,Glycation ,Genetics ,medicine ,Tubular basement membrane ,Advanced glycation end-products ,Molecular Biology ,lcsh:QH301-705.5 ,Physiological function ,Diabetic kidney ,Mechanical models ,Chemistry ,Diabetes ,Cell Biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,Elastic modulus - Abstract
The mechanical properties of the extracellular matrix (ECM) are important in maintaining normal physiological function, and changes in ECM mechanics drive disease. The biochemical structure of the ECM is modified with aging and in diseases such as diabetes. One mechanism of ECM modification is the non-enzymatic reaction between sugars and ECM proteins resulting in formation of advanced glycation end products (AGEs). Some AGE reactions result in formation of molecular crosslinks within or between matrix proteins, but it is not clear how sugar-mediated biochemical modification of the ECM translates to changes in kidney ECM mechanical properties. AGE-mediated changes in ECM mechanics may have pathological consequences in diabetic kidney disease. To determine how sugars alter the mechanical properties of the kidney ECM, we employ custom methodologies to evaluate the mechanical properties of isolated tubular basement membrane (TBM) and glomerular ECM. Results show that the mechanical properties of TBM and glomerular ECM stiffness were altered by incubation in glucose and ribose. Mechanical behavior of TBM and glomerular ECM were further evaluated using mechanical models for hyperelastic materials in tension and compression. Increased ECM stiffness following sugar modification corresponded to increased crosslinking as determined by ECM fluorescence and reduced pepsin extractability of sugar modified ECM. These results show that sugar-induced modifications significantly affect the mechanical properties of kidney ECM. AGE-mediated changes in ECM mechanics may be important in progression of chronic diseases including diabetic kidney disease., Highlights • Sugars modify the mechanical properties of the kidney extracellular matrix. • Sugars increase matrix crosslinking and stiffness. • A novel method was used to measure glomerular matrix stiffness. • Non-linear mechanical models describe kidney matrix mechanics.
- Published
- 2020